34.11:
Cells Coordinate Growth and Proliferation
Cell size is a crucial factor in most fundamental processes, such as nutrient transport.
In an abnormally large cell, nutrients have to move longer distances to spread throughout the cell. As a result, nutrient diffusion becomes slow, causing the cell to die from nutrient starvation.
Therefore, a healthy cell regulates its growth at cell cycle checkpoints- usually at the G1/S phase transition or the G2/M phase transition.
These checkpoints enable the cell to monitor its size and regulate the timing of cell division, thereby ensuring the daughter cells have a consistent size- a phenomenon called size homeostasis.
Unicellular organisms, such as yeast, are frequently used as model organisms to study size homeostasis.
A budding yeast cell divides asymmetrically, producing a larger mother cell and a smaller daughter cell.
The larger mother cell quickly grows to its critical size and passes the size checkpoint at the G1/S phase transition.
In contrast, the smaller daughter cell has a large size gap to achieve and therefore spends more time growing in the G1 phase.
At the early G1 phase, protein complexes SBF and MBF, the cell cycle-promoting transcription factors are usually bound and inhibited by a repressor protein called Whi5, thereby preventing cell cycle transition.
The cell cycle reactivation depends on a sizer protein called Cln3, a G1 cyclin whose concentration increases proportionally with the cell size.
When the cell attains its target size, Cln3 reaches a critical concentration and forms a complex with cyclin-dependent kinase-1 or Cdk1, a key activator of cell cycle promoting factors.
The active Cln3-Cdk1 complex then phosphorylates Whi5 at multiple sites to release active SBF and MBF transcription factors that trigger G1/S phase transition genes involved in vital processes such as bud initiation and DNA replication.
Activation of these transition events enables the cell to pass the size checkpoint and proceed through other stages of the cell cycle.
34.11:
Cells Coordinate Growth and Proliferation
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth, non-dividing cells in adults regulate cell size depending on their metabolic states.
In adults, the size of non-dividing muscle cells varies depending on the environmental conditions and nutritional state. Regular physical workout causes adult muscle cells to enlarge as individual myocytes grow in size due to the absence of proliferation in the myocytes themselves or the muscle stem cell population. In contrast, nutrient deficiency can severely damage the muscle cells. The size of muscle cells depends on the balance between the anabolic pathway that increases the cell size and the catabolic pathway that degrades intracellular proteins causing the cell size to reduce.
The anabolic or IFF/PI3K/AKT/mTORC1 pathway involves mTORC1 signaling that leads to protein synthesis, giving rise to a condition called- muscle cell hypertrophy. However, this increase in cell size is temporary. For the cells to maintain their size, one must regularly exercise for continuous mTORC1 signaling. Lack of exercise, starvation, or certain muscle disease triggers a catabolic pathway or Myostatin/SMAD2/3 for protein degradation. The degradation of proteins mobilizes amino acids to other cells of the body, thus, reducing the size of the skeletal muscle cells.
Suggested Reading
- Lloyd, Alison C. "The regulation of cell size." Cell 154, no. 6 (2013): 1194-1205.
- Jorgensen, Paul, and Mike Tyers. "How cells coordinate growth and division." Current Biology 14, no. 23 (2004): R1014-R1027.